Laboratory of Immune Cell Biology, Center for Cancer Research (CCR), NCI, NIH, Bethesda, MD 20892-4259, USA.
Eur J Immunol. 2010 Sep;40(9):2385-90. doi: 10.1002/eji.201040534.
While most CD4(+) T cells are MHC class II-restricted, a small subset, including the CD1d-restricted 'invariant' NKT (iNKT) cells, are selected on non-classical MHC-I or MHC-I-like molecules. We previously showed that the sequential activity of two zinc finger transcription factors, Gata3 and Thpok, promotes the differentiation of conventional, MHC II-restricted thymocytes into CD4(+) T cells. In the current study, we show that a Gata3-Thpok cascade is required for the differentiation of CD4(+) iNKT cells. Gata3 is required for iNKT cells to express Thpok, whereas Thpok is needed for proper NKT cell differentiation, and notably for NKT cells to maintain CD4 and terminate CD8 expression. These findings identify the sequential activity of Gata3 and Thpok as a hallmark of CD4(+) T-cell differentiation, regardless of MHC restriction.
虽然大多数 CD4(+) T 细胞受到 MHC Ⅱ类限制，但一小部分细胞，包括 CD1d 限制的“不变”自然杀伤 T(iNKT)细胞，是在非经典 MHC-I 或 MHC-I 样分子上选择的。我们之前表明，两个锌指转录因子 Gata3 和 Thpok 的顺序活性促进了常规 MHC II 限制的胸腺细胞向 CD4(+) T 细胞的分化。在本研究中，我们表明 Gata3-Thpok 级联对于 CD4(+) iNKT 细胞的分化是必需的。Gata3 对于 iNKT 细胞表达 Thpok 是必需的，而 Thpok 对于 NKT 细胞的适当分化是必需的，特别是对于 NKT 细胞维持 CD4 和终止 CD8 表达是必需的。这些发现确定了 Gata3 和 Thpok 的顺序活性是 CD4(+) T 细胞分化的标志，而与 MHC 限制无关。
